The 1,3-dithiol-2-ide carbanion
This review covers the 1,3-dithiol-2-ide structural unit in relation to the dual electronic character of dithiafulvene and in relation to using it as a synthetic building block for constructing for example extended tetrathiafulvalenes.
Stereogenic and conformational properties of medium-ring benzo-fused N-heterocycle atropisomers
By examining the various contributions to the conformational and stereogenic stability of medium-sized benzo-fused N-heterocyclic atropisomers, this review serves to aid the design, synthesis and study of these pharmaceutically relevant heterocycles.
Modelling biocompatible ionic liquids based on organic acids and amino acids: challenges for computational models and future perspectives
From isolated molecules to the bulk phase: building models of biocompatible ionic liquids.
Computational evidence of glycosyl cations
This review covers recent computational studies evidencing the presence of glycosyl cations as real intermediates in several glycosylation reactions.
The role of intermolecular forces in ionic reactions: the solvent effect, ion-pairing, aggregates and structured environment
A general view of the medium effects on ionic reactions involves the solvent effect, ion pairing, formation of aggregates and structured environment.
A theoretical review for novel Lewis base amine/imine-catalyzed reactions
Recent advances in computational investigations of Lewis base amine/imine-catalyzed reactions have been systematically summarized and reviewed for the first time.
Optical purity, enantiomeric excess and the Horeau effect
Optical purity (op) and enantiomeric excess (ee) become equal when either heterochiral dimerization constant is twice that of homochiral dimerization constant or specific rotations of monomer and dimer are equal.
Synthetic and mechanistic aspects of sulfonyl migrations
Sulfonyl migrations, frequently described as ‘unusual’ or ‘unexpected’, from the last 20 years, including 1,2-, 1,3-, 1,4-, 1,5-, 1,6- and 1,7-sulfonyl shifts, through either radical or polar processes, either inter- or intramolecularly are reviewed.
Mechanistic knowledge and noncovalent interactions as the key features for enantioselective catalysed multicomponent reactions: a critical review
This critical short review focuses on some key features which determine successful enantioselective catalysed multicomponent reactions (MCRs) and are typically underappreciated in the literature.
The importance of N-heterocyclic carbene basicity in organocatalysis
This review highlights the importance of N-heterocyclic carbene (NHC) basicity for transformations in which NHCs are used as catalysts.
Water clusters as bifunctional catalysts in organic chemistry: the hydrolysis of oxirane and its methyl derivatives
This contribution explores the bifunctional catalytic activity of water clusters ((H2O)n with n = 1–5) in organic chemistry similar to that observed in the formation of H2SO4 in acid rain.
Mechanism of Pd-catalysed C(sp3)–H arylation of thioethers with Ag(I) additives
The mechanism of Pd-catalysed γ-C(sp3)–H arylation of thioethers has been disclosed, wherein all steps proceed through the heterodimeric Pd–Ag pathway.
Understanding the sigmatropic shifts of cyclopenta-2,4-dien-1-yltrimethylsilane in its Diels–Alder addition
Investigation on the dynamic processes of 1-(C5H5)Si(Me)3 in its Diels–Alder addition showed that Si(Me)3 migration is the dominant factor and hydrogen shifts are negligible.
On the reciprocal relationship between σ-hole bonding and (anti)aromaticity gain in ketocyclopolyenes
σ-Hole bonding interactions (e.g., tetrel, pnictogen, chalcogen, and halogen bonding) can polarize π-electrons to enhance cyclic [4n] π-electron delocalization (i.e., antiaromaticity gain) or cyclic [4n + 2] π-electron delocalization (i.e., aromaticity gain).
Divergent pathway and reactivity control of intramolecular arene C–H vinylation by vinyl cations
A computational study revealed the mechanistic details and controlling factors of reactivity in intramolecular C–H vinylation through a vinyl cation intermediate.
The optimal DFT approach in DP4 NMR structure analysis – pushing the limits of relative configuration elucidation
What computational methods should be used to achieve the most reliable result in computational structure elucidation? A study on the effect of quality and quantity of geometries on computational NMR structure elucidation performance is reported.
Mechanism of nitrones and allenoates cascade reactions for the synthesis of dihydro[1,2-a]indoles
Quantum mechanical calculations (DLPNO-CCSD(T) and M06-2X) are employed to gain insights into the mechanism and selectivity in the catalytic synthesis of dihydropyrido[1,2-a]indoles from the cascade reaction between nitrones and allenes.
A Viedma ripening route to an enantiopure building block for Levetiracetam and Brivaracetam
A simple route to enantiomerically pure (S)-2-aminobutyramide – the chiral component of the anti-epileptic drugs Levetiracetam and Brivaracetam has been developed. This approach is based on the rational design and application of a Viedma ripening process. The practical potential of the process is demonstrated on a large scale.
Superelectrophilic activation of 1-nitronaphthalene in the presence of aluminum chloride. Reactions with benzene and cyclohexane
Aluminum chloride was successfully used instead of liquid superacids to mediate selective reactions of 1-nitronaphthalene with benzene and cyclohexane.
Experimental evidence for the formation of cationic intermediates during iodine(III)-mediated oxidative dearomatization of phenols
Hammett analysis reveals iodine(III)-mediated oxidative dearomatization reactions proceed through cationic intermediates and not direct nucleophilic attack on an activated phenol.
On the dual reactivity of a Janus-type mesoionic dipole: experiments and theoretical validation
A mesoionic bicycle, easily synthesized from a proteinogenic amino acid, L-leucine, behaves as both thiazolium-olate and diazolium-olate dipoles, as unveiled by its dipolar cycloadditions.
A “cross-stitched” peptide with improved helicity and proteolytic stability
Peptide “cross-stitching” maintains binding affinity and can enhance helical and proteolytic stability.
Predicting the catalytic activity of azolium-based halogen bond donors: an experimentally-verified theoretical study
The most promising types of iodoazolium compounds exhibiting high catalytic activity toward halogen abstraction and carbonyl activation are highlighted.
Biological halogen bonds in protein–ligand complexes: a combined QTAIM and NCIPlot study in four representative cases
In this study, the PDB has been inspected for the analysis of HaBs in biological systems, highlighting their importance in four different protein–ligand systems.
Synthesis of homochiral sulfanyl- and sulfoxide-substituted naphthyltriazoles and study of the conformational stability
Novel homochiral sulfanyl-substituted naphthyltriazoles are synthesized via the triazolization reaction, and their rotational stability is studied in detail.
In Silico Characterization and Prediction of Thiourea-like Neutral Bidentate Halogen Bond Catalysts
Structural and mechanistic insight into DNA bending by antitumour calicheamicins
Atomistic molecular dynamics simulations shed structural light on the curvature inflicted on DNA upon binding of calicheamicin ε to high-affinity and low-affinity target sites.
The mechanism of conversion of substituted glycals to chiral acenes via Diels–Alder reaction: a computational study
Transformation of substituted glycals to chiral fused aromatic cores using DFT calculations reveal that the base catalyzed reaction is favorable over sigmatropic [1,5] hydrogen shift and the product formation is governed by aromaticity.
Accelerating the optimization of enzyme-catalyzed synthesis conditions via machine learning and reactivity descriptors
Enzyme-catalyzed synthesis reactions are of crucial importance for a wide range of applications.
An examination of the relationship between molecular dipole moment and blood-gas partition for common anaesthetic gases
The overall molecular dipole moments calculated for some common fluorinated anaesthetics correlate with the respective blood-gas partition. This finding may aid the design of novel last-generation anaesthetics.
The inverting mechanism of the metal ion-independent LanGT2: the first step to understand the glycosylation of natural product antibiotic precursors through QM/MM simulations
Glycosyltransferases (GTs) from the GT1 family are responsible for the glycosylation of various important organic structures such as terpenes, steroids and peptide antibiotics, making it one of the most intensely studied families of GTs.
Structural variation of protein–ligand complexes of the first bromodomain of BRD4
The importance of the water network in BRD4-BD1 complexes is illustrated using molecular docking and absolute free energy perturbation simulations. 82% of the ligand poses were better predicted when including water molecules as part of the receptor.
Tuning the exchange dynamics of boronic acid hydrazones and oximes with pH and redox control
Hydrazones and oximes with proximal boronic acids undergo facile exchange, which can be sped up or slowed down with pH control or abolished with oxidation.
Wavelength dependent photochemistry of BODIPY–phenols and their applications in the fluorescent labeling of proteins
The molecules undergo wavelength dependent photochemistry, since photodeamination to QMs takes place only upon excitation to higher excited singlet states, showing unusual anti-Kasha photochemical reactivity.
Mannosylated adamantane-containing desmuramyl peptide recognition by the NOD2 receptor: a molecular dynamics study
The dipeptide isoGln moiety of ManAdDMP significantly contributes to the binding to the NOD2 receptor. Loops 2 and 7 are important for ligand recognition and could be useful for further investigation of NOD2 activation/inhibition.
A computational study of site-selective hydrogen abstraction by sulfate radical anion
Ab initio and DFT calculations revealed that β-hydrogen abstraction would be favourable, which supports experimental findings (i.e. β-selective abstraction).
How is vitamin B1 oxidized to thiochrome? Elementary processes revealed by a DFT study
The oxidation mechanism of thiamine (vitamin B1) to thiochrome was investigated by DFT calculations for reaction models, thiamine + oxidant + (H2O)8. A key thiazolone intermediate (Int2) was commonly found to intervene during the oxidation.
VRAI-selectivity: calculation of selectivity beyond transition state theory
We present the VRAI-selectivity program which predicts the major product and selectivity not only for transition-state controlled reactions but also for processes controlled by reaction dynamics.
Mechanistic studies of Cp*Ir(III)/Cp*Rh(III)-catalyzed branch-selective allylic C–H amidation: why is Cp*Ir(III) superior to Cp*Rh(III)?
DFT mechanistic investigations uncovered the origins of the reactivity and regioselectivity of Cp*Ir(III)/Cp*Rh(III)-catalyzed allylic C–H amidation reactions.
Studies on chemoselective synthesis of 1,4- and 1,2-dihydropyridine derivatives by a Hantzsch-like reaction: a combined experimental and DFT study
In the experimental process of preparing 1,4-DHP by a Hantzsch-like reaction, it was found that a by-product named 1,2-DHP was produced.
Chemisorption of CO2 by diamine-tetraamido macrocyclic motifs: a theoretical study
A series of diamine-tetraamido macrocyclic molecules with different organic linkers are explored as potential CO2 capturing agents using quantum chemical calculations.
Understanding the mechanism of the chiral phosphoric acid-catalyzed aza-Cope rearrangement
Using Density Functional Theory, the mechanism of the enantioselective phosphoric acid-catalyzed aza-Cope rearrangement was investigated. Stabilization of the preferred reaction pathway was rationalized by studying the non-bonding interactions between substrate and catalyst.
Catalytic and non-catalytic hydroboration of carbonyls: quantum-chemical studies
The present paper examines both catalyst-free and KF-mediated hydroboration of carbonyl compounds with the use of quantum-chemical methods.
Triplet stabilization for enhanced drug photorelease from sunscreen-based photocages
The importance of the relative triplet excited state energies of avobenzone (our phenacyl-like photolabile group) and ketoprofen (our photocaged drug) has been demonstrated by means of spectroscopic experiments and theoretical calculations.
Regioselectivity and stereoselectivity of intramolecular [2 + 2] photocycloaddition catalyzed by chiral thioxanthone: a quantum chemical study
Chiral photosensitizer-catalyzed stereoselective olefin cyclization has shown its significance in organic synthesis.
QM/MM and molecular dynamics investigation of the mechanism of covalent inhibition of TAK1 kinase
This work describes a study which elucidates the reaction mechanism of TAK1 kinase, an important target implicated in aberrant cellular signaling, towards irreversible inhibitors using hybrid quantum mechanical/molecular mechanical methods.
Role of substituents in the Hofmann–Löffler–Freytag reaction. A quantum-chemical case study on nicotine synthesis
The Hofmann–Löffler–Freytag (HLF) reaction can be successfully used to synthesize saturated heterocyclic nitrogen-containing nature-derived pharmaceuticals such as nicotine and its derivatives.
Unusual temperature-sensitive protonation behaviour of 4-(dimethylamino)pyridine
An unusually strong impact of temperature on the protonation degree of DMAP in strong acid solutions has been found.
Kinetic and structure–activity studies of the triazolium ion-catalysed benzoin condensation
An initial rate evaluation of the triazolium-catalysed benzoin condensation permitted a Hammett structure–activity analysis providing insight into the rate-limiting step.
Using experimental and computational approaches to probe an unusual carbon–carbon bond cleavage observed in the synthesis of benzimidazole N-oxides
An unusual carbon–carbon bond-cleavage is explored using a combination of experimental and computational studies.
Activation barriers in Class F G protein-coupled receptors revealed by umbrella sampling simulations
Molecular simulations reveal energetic barriers to Class F GPCR activation.
Quantum chemical (QM:MM) investigation of the mechanism of enzymatic reaction of tryptamine and N,N-dimethyltryptamine with monoamine oxidase A
Oxidation mechanism pathways of psychedelic N,N-dimethyltryptamine, or the so-called “spirit molecule”, with monoamine oxidase A enzyme were determined.
Theoretical study on reaction mechanism of phosphate-catalysed N–S acyl transfer of N-sulfanylethylanilide (SEAlide)
Reaction mechanisms of phosphate-catalyzed N–S acyl transfer of N-sulfanylethylanilide (SEAlide) were elucidated by DFT calculations and NCI analyses.
The unimolecular dissociation of magnesium chloride squarate (ClMgC4O4−) and reductive cyclooligomerisation of CO on magnesium
Cyclooligomerisation to squarate is initiated by the coupling of two CO units in MgCl−.
Experimental and computational evidence on gold-catalyzed regioselective hydration of phthalimido-protected propargylamines: an entry to β-amino ketones
Gold-catalyzed regioselective hydration of phthalimido-protected propargylamines.
Regioselectivity in the adiabatic photocleavage of DNA-based oxetanes
The photocleavage of oxetanes composed of benzophenone and uracil or thymine derivatives takes place through an adiabatic process, which is markedly affected by the oxetane regiochemistry and by the nucleobase substitutions at positions 1 and 5.
A mechanistic study on Cu(I) catalyzed carboxylation of the C–F bond with CO2: a DFT study
Cu(I) catalyzed carboxylation of the C–F bond is an excellent method for construction of complex fluoroacrylate compounds with high regioselectivity. Here, theoretical calculations were carried out to investigate the detailed mechanism and origin of regioselectivity.
Raise the anchor! Synthesis, X-ray and NMR characterization of 1,3,5-triazinanes with an axial tert-butyl group
N-t-Bu-N′,N′′-Disulfonamide-1,3,5-triazinanes were synthesized and studied by X-ray single crystal structure analysis and dynamic low-temperature NMR.
How the combination of PhIO and I2 provides a species responsible for conducting organic reactions through radical mechanisms
This contribution provides an answer to the long-standing question of how organic radicals are produced by the PhIO/I2 system and how the ensuing radicals are oxidized by the same system to yield the organic products.
Microwave-assisted nucleophilic degradation of organophosphorus pesticides in propylene carbonate
Degradation of organophosphorus pesticides was achieved by using microwaves, an ionic liquid and propylene carbonate.
Guest-induced supramolecular chirality transfer in pseudorotaxanes: experimental and computational study
We constructed several pseudorotaxanes via chiral binaphthalene crown ethers and achiral ammonium salts, and found that the binaphthalene groups can induce new CD signals only in the pseudorotaxane between the hosts and the guest with anthryl.
How inverting β-1,4-galactosyltransferase-1 can quench a high charge of the by-product UDP3− in catalysis: a QM/MM study of enzymatic reaction with native and UDP-5′ thio galactose substrates
The function of Asp252 in the catalysis of β-1,4-galactosyltransferase-1 may be the stabilization of a high charge of the by-product UDP3− by a substrate-assisted proton transfer reaction.
Influence of a 4′-substituent on the efficiency of flavonol-based fluorescent indicators of β-glycosidase activity
Fluorescent probes for glycosidases, based on the excited-state intramolecular proton transfer (ESIPT) phenomenon, are presented.
A simpler method affords evaluation of π stabilization by phenylalanine of several biochemical carbocations
Simple models based on measurements taken from X-ray structures of relevant active sites are used to evaluate π stabilization by phenylalanine of several biochemical carbocations.
Computational investigations of NHC-backbone configurations for applications in organocatalytic umpolung reactions
Computational modeling and orbital analyses reveal enhanced catalytic properties based on N-heterocyclic carbene backbone modifications.
The effect of bisimidazolium-based ionic liquids on a bimolecular substitution process. Are two head(group)s better than one?
Bisimidazolium-based ionic liquids generally result in greater rate constants than the corresponding monocationic salts. The effect depends on the length of the bridging chain; likely due to a change in the mode of interactions in solution.
Oxidative damage of proline residues by nitrate radicals (NO3˙): a kinetic and product study
Kinetic studies in acetonitrile revealed that proline residues in peptides are considerably protected against radical-induced oxidative damage by the neighbouring peptide bonds, compared with the single amino acid.
Deconvolution of fast exchange equilibrium states in NMR spectroscopy using virtual reference standards and probability theory
DFT–GIAO calculations combined with probability theory enable accurate prediction of fast exchange equilibrium states based on one experimental NMR dataset.
Mechanistic insights into Smiles rearrangement. Focus on π–π stacking interactions along the radical cascade
The synthesis of new arene and heteroarene scaffolds of therapeutic interest has generated a renewed interest in the domino radical cyclisation–Smiles.
Decomplexation as a rate limitation in the thiol-Michael addition of N-acrylamides
Experimental and computational agreement highlights rate-limiting “product decomplexation” and functional group effects in the thiol-Michael addition, utilized for sequence-defined oligomers.
About this collection
The latest articles published in Organic and Biomolecular Chemistry related to mechanistic, computational & physical organic chemistry research.